Strength-duration properties and excitability of motor and sensory axons across different target thresholds.

The present series of studies aimed to investigate the biophysical basis underlying differences in behavior between motor and sensory axons at different target response levels. In 24 healthy individuals, axonal excitability protocols measured strength-duration properties and latent addition across several axonal populations, with target amplitudes set at 10%, 20%, 40%, and 60%. Strength-duration time constants (SDTCs) were typically longer at lower target levels for both motor and sensory axons. Threshold change at 0.2 ms during assessment of latent addition, representing a persistent Na+ current (Nap), was higher in sensory axons. Passive membrane properties were not different across target levels. Significant relationships were evident between the threshold change at 0.2 ms and SDTC across all target levels for motor and sensory axons. These differences were explored using mathematical modeling of excitability data. With decreasing target size, as the internodal leak conductance increased in sensory axons, the Barrett-Barrett conductance decreased, whereas the hyperpolarization-activated cation current (Ih) channels became more depolarized. A similar pattern was observed in motor axons. As such, it was concluded that Nap was not responsible for the differences observed in SDTC between different target levels, although within specific target levels, Nap changes contributed to the variability of SDTC. This study provides a comprehensive assessment of Nap current, SDTC, and outlines key factors operating at different target levels in motor and sensory axons. Findings from the present study may point to the contributing factors of symptom development in human neuropathy.NEW & NOTEWORTHY This study provides a comprehensive assessment concerning the strength-duration behavior of motor and sensory axons at differing target levels of the compound nerve response. Strength-duration time constant was increased at lower target response levels particularly for sensory axons, whereas threshold change at 0.2 ms and passive membrane properties were not different. The results have established templates for axonal behavior in normal human axons, demonstrating altered adaptive responses, presumably secondary to different patterns of nerve activation.

Diagnostic utility of transcranial magnetic stimulation for neurodegenerative disease: a critical review / Utilidade diagnóstica da estimulação magnética transcraniana para doenças neurodegenerativas: uma revisão crítica

ABSTRACT. Neurodegenerative diseases pose significant challenges due to their impact on brain structure, function, and cognition. As life expectancy rises, the prevalence of these disorders is rapidly increasing, resulting in substantial personal, familial, and societal burdens. Efforts have been made to optimize the diagnostic and therapeutic processes, primarily focusing on clinical, cognitive, and imaging characterization. However, the emergence of non-invasive brain stimulation techniques, specifically transcranial magnetic stimulation (TMS), offers unique functional insights and diagnostic potential. TMS allows direct evaluation of brain function, providing valuable information inaccessible through other methods. This review aims to summarize the current and potential diagnostic utility of TMS in investigating neurodegenerative diseases, highlighting its relevance to the field of cognitive neuroscience. The findings presented herein contribute to the growing body of research focused on improving our understanding and management of these debilitating conditions, particularly in regions with limited resources and a pressing need for innovative approaches.

RESUMO. As doenças neurodegenerativas representam desafio significativo por seu impacto na estrutura cerebral, função e cognição. À medida que a expectativa de vida aumenta, a prevalência dessas doenças cresce rapidamente, resultando em substanciais encargos pessoais, familiares e sociais. Esforços têm sido feitos para otimizar os processos diagnósticos e terapêuticos, com foco principal na caracterização clínica, cognitiva e de imagem. No entanto, o surgimento de técnicas de estimulação cerebral não invasivas, especificamente a estimulação magnética transcraniana (EMT), oferece compreensão funcional e potencial diagnóstico únicos. A TMS permite a avaliação direta da função cerebral, fornecendo informações valiosas inacessíveis por outros métodos. Esta revisão teve como objetivo resumir a utilidade diagnóstica atual e potencial da EMT na investigação de doenças neurodegenerativas, destacando sua relevância para o campo da neurociência cognitiva. As conclusões aqui apresentadas contribuem para o crescente corpo de investigação centrado na melhoria da nossa compreensão e gestão dessas condições debilitantes, particularmente em regiões com recursos limitados e necessidade premente de abordagens inovadoras.

Diagnostic utility of transcranial magnetic stimulation for neurodegenerative disease: a critical review.

Neurodegenerative diseases pose significant challenges due to their impact on brain structure, function, and cognition. As life expectancy rises, the prevalence of these disorders is rapidly increasing, resulting in substantial personal, familial, and societal burdens. Efforts have been made to optimize the diagnostic and therapeutic processes, primarily focusing on clinical, cognitive, and imaging characterization. However, the emergence of non-invasive brain stimulation techniques, specifically transcranial magnetic stimulation (TMS), offers unique functional insights and diagnostic potential. TMS allows direct evaluation of brain function, providing valuable information inaccessible through other methods. This review aims to summarize the current and potential diagnostic utility of TMS in investigating neurodegenerative diseases, highlighting its relevance to the field of cognitive neuroscience. The findings presented herein contribute to the growing body of research focused on improving our understanding and management of these debilitating conditions, particularly in regions with limited resources and a pressing need for innovative approaches.

As doenças neurodegenerativas representam desafio significativo por seu impacto na estrutura cerebral, função e cognição. À medida que a expectativa de vida aumenta, a prevalência dessas doenças cresce rapidamente, resultando em substanciais encargos pessoais, familiares e sociais. Esforços têm sido feitos para otimizar os processos diagnósticos e terapêuticos, com foco principal na caracterização clínica, cognitiva e de imagem. No entanto, o surgimento de técnicas de estimulação cerebral não invasivas, especificamente a estimulação magnética transcraniana (EMT), oferece compreensão funcional e potencial diagnóstico únicos. A TMS permite a avaliação direta da função cerebral, fornecendo informações valiosas inacessíveis por outros métodos. Esta revisão teve como objetivo resumir a utilidade diagnóstica atual e potencial da EMT na investigação de doenças neurodegenerativas, destacando sua relevância para o campo da neurociência cognitiva. As conclusões aqui apresentadas contribuem para o crescente corpo de investigação centrado na melhoria da nossa compreensão e gestão dessas condições debilitantes, particularmente em regiões com recursos limitados e necessidade premente de abordagens inovadoras.

Manejo multidisciplinario y avances terapéuticos en la esclerosis lateral amiotrófica / Multidisciplinary care and therapeutic advances in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the motor system, resulting in progressive weakness and muscle wasting. Despite the tremendous advances in physiopathological and clinical characterization, we do not have a curative treatment yet. The progressive and fatal course of ALS makes its management particularly complex and challenging given the diversity of symptoms presenting during the disease progression. The main goal in the treatment of ALS patients is to minimize morbidity and maximize the quality of life. Currently, a series of therapeutic interventions improve the quality of life and prolong survival, including multidisciplinary care, respiratory management, and disease-modifying therapy. Within the supportive interventions, weight maintenance through nutritional and metabolic support is critical. In addition, the management of neuropsychiatric manifestations and preservation of communicative capacity before speech loss are also crucial. Lastly, early palliative care intervention is essential to optimize symptomatic management. Anticipatory guidelines to face the inevitable patient deterioration should be devised. This article updates the main therapeutic strategies used in these patients, including evolving clinical trials with promising novel therapies.

[Degenerative cervical myelopathy]. / Mielopatía cervical degenerativa: una patología cada vez más frecuente y que requiere diagnóstico y manejo precoz.

Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction in adults. Its prevalence is increasing as a result of population aging. The diagnosis of DCM is often delayed or overlooked, resulting in secondary neurologic morbidity. The natural course of DCM typically presents as a gradual neurological deterioration, with symptoms ranging from muscle weakness to complete paralysis, with variable degrees of sensory deficits and sphincter dysfunction. Magnetic resonance imaging (MRI) and electrophysiological studies allow the assessment of spinal cord function and its structural damage to determine treatment and clinical outcomes. All patients with signs and symptoms consistent with DCM should be referred to a spine surgeon for assessment and tailored treatment. Those patients with mild DCM can be managed non-operatively but require close monitoring and education about potentially alarming signs and symptoms. Surgery is not currently recommended for asymptomatic patients with evidence of spinal cord compression or cervical spinal stenosis on MRI, but they require a structured follow-up. Patients with moderate or severe DCM require surgical decompression to avoid further progression. The objective of this review is to raise awareness of degenerative cervical myelopathy and its increasing prevalence as well as to aid non-surgical healthcare workers for a timely diagnosis and management of this disabling condition.

Polineuropatía por amiloidosis por transtiretina de inicio tardío. Caso clínico / Late-onset hereditary transthyretin amyloidosis with polyneuropathy. Report of one case

Hereditary transthyretin amyloidosis is a multisystemic autosomal dominant genetic disorder characterized by progressive distal sensory-motor polyneuropathy or restrictive cardiomyopathy, secondary to amyloid deposits. Its pathogenesis lies in the TTR gene mutation, and the Val50Met mutation is the most frequent. Patients have significant differences in the onset and severity of clinical presentation according to their country of origin. The diagnosis of this pathology is complex, even more in countries where it is not considered endemic. However, early suspicion and management are essential to improve survival and avoid unnecessary diagnostic and therapeutic strategies. We report a 69-year-old woman who presented a sensory-motor polyneuropathy, predominantly sensory, associated with distal neuropathic pain and bilateral vitritis. The history of her Italian father with polyneuropathy of unspecified etiology stood out. A vitreous biopsy identified amyloid substance deposits (congo red positive). These were also confirmed on a superficial peroneal nerve biopsy. During the etiological study of her polyneuropathy, an increased Kappa/Lambda index of 2.55 mg/L stood out. Therefore, light chain amyloidosis was suspected, and chemotherapy treatment was indicated without favorable response. After 10 years of progressive neurological and ophthalmological involvement, a genetic study confirmed the first case of late-onset hereditary transthyretin amyloidosis Val50Met with polyneuropathy in Chile.

Mielopatía cervical degenerativa: una patología cada vez más frecuente y que requiere diagnóstico y manejo precoz

Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction in adults. Its prevalence is increasing as a result of population aging. The diagnosis of DCM is often delayed or overlooked, resulting in secondary neurologic morbidity. The natural course of DCM typically presents as a gradual neurological deterioration, with symptoms ranging from muscle weakness to complete paralysis, with variable degrees of sensory deficits and sphincter dysfunction. Magnetic resonance imaging (MRI) and electrophysiological studies allow the assessment of spinal cord function and its structural damage to determine treatment and clinical outcomes. All patients with signs and symptoms consistent with DCM should be referred to a spine surgeon for assessment and tailored treatment. Those patients with mild DCM can be managed non-operatively but require close monitoring and education about potentially alarming signs and symptoms. Surgery is not currently recommended for asymptomatic patients with evidence of spinal cord compression or cervical spinal stenosis on MRI, but they require a structured follow-up. Patients with moderate or severe DCM require surgical decompression to avoid further progression. The objective of this review is to raise awareness of degenerative cervical myelopathy and its increasing prevalence as well as to aid non-surgical healthcare workers for a timely diagnosis and management of this disabling condition.

[Late-onset hereditary transthyretin amyloidosis with polyneuropathy. Report of one case]. / Polineuropatía por amiloidosis por transtiretina de inicio tardío. Caso clínico.

Hereditary transthyretin amyloidosis is a multisystemic autosomal dominant genetic disorder characterized by progressive distal sensory-motor polyneuropathy or restrictive cardiomyopathy, secondary to amyloid deposits. Its pathogenesis lies in the TTR gene mutation, and the Val50Met mutation is the most frequent. Patients have significant differences in the onset and severity of clinical presentation according to their country of origin. The diagnosis of this pathology is complex, even more in countries where it is not considered endemic. However, early suspicion and management are essential to improve survival and avoid unnecessary diagnostic and therapeutic strategies. We report a 69-year-old woman who presented a sensory-motor polyneuropathy, predominantly sensory, associated with distal neuropathic pain and bilateral vitritis. The history of her Italian father with polyneuropathy of unspecified etiology stood out. A vitreous biopsy identified amyloid substance deposits (congo red positive). These were also confirmed on a superficial peroneal nerve biopsy. During the etiological study of her polyneuropathy, an increased Kappa/Lambda index of 2.55 mg/L stood out. Therefore, light chain amyloidosis was suspected, and chemotherapy treatment was indicated without favorable response. After 10 years of progressive neurological and ophthalmological involvement, a genetic study confirmed the first case of late-onset hereditary transthyretin amyloidosis Val50Met with polyneuropathy in Chile.

[Multidisciplinary care and therapeutic advances in amyotrophic lateral sclerosis]. / Manejo multidisciplinario y avances terapéuticos en la esclerosis lateral amiotrófica.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the motor system, resulting in progressive weakness and muscle wasting. Despite the tremendous advances in physiopathological and clinical characterization, we do not have a curative treatment yet. The progressive and fatal course of ALS makes its management particularly complex and challenging given the diversity of symptoms presenting during the disease progression. The main goal in the treatment of ALS patients is to minimize morbidity and maximize the quality of life. Currently, a series of therapeutic interventions improve the quality of life and prolong survival, including multidisciplinary care, respiratory management, and disease-modifying therapy. Within the supportive interventions, weight maintenance through nutritional and metabolic support is critical. In addition, the management of neuropsychiatric manifestations and preservation of communicative capacity before speech loss are also crucial. Lastly, early palliative care intervention is essential to optimize symptomatic management. Anticipatory guidelines to face the inevitable patient deterioration should be devised. This article updates the main therapeutic strategies used in these patients, including evolving clinical trials with promising novel therapies.

Fasciculaciones y calambres: bases fisiológicas y enfrentamiento clínico de un fenómeno complejo

Fasciculations and cramps originate in the motor unit, a functional unit that includes the lower motor neuron and their innervated muscle fibres. Both are common complaints in outpatient practice. These symptoms can be secondary to neurological or medical pathology, presenting a broad differential diagnosis and a complex approach. Recent neurophysiological studies have increased the knowledge of their origin mainly in amyotrophic lateral sclerosis. The symptomatic management of fasciculations and cramps depends on their etiology and includes pharmacological and non-pharmacological treatments. This article aims to present an updated review of the most relevant aspects of physiopathology, clinical approach, and differential diagnosis of both phenomena.

[Subacute encephalopathy associated with relapsing polychondritis. Report of one case]. / Encefalopatía subaguda en una paciente con policondritis recidivante. Caso clínico.

Relapsing polychondritis (RP) is a rare multisystemic autoimmune disorder characterized by the inflammation and destruction of cartilages, with preference for auricular, nasal and laryngotracheal cartilages. RP may also affect proteoglycan-rich structures, such as, blood vessels, eyes, kidneys, and heart. The central nervous system (CNS) is involved in less than 3% of patients. We report a 32-year-old female with RP associated with a progressive subacute encephalopathy characterized by behavioral disturbances, auditory and visual hallucinations. The EEG showed generalized slow activity and a mononuclear pleocytosis with increased protein was found in the cerebrospinal fluid. The brain magnetic resonance imaging showed multiple supra and infratentorial nodular inflammatory lesions. After initiating treatment with corticosteroids and cyclophosphamide, a significant improvement in chondritis and neurological status was observed.

Electroencefalograma cuantitativo en la predicción precoz de la isquemia cerebral tardía en hemorragia subaracnoidea aneurismática: reporte de un caso / Quantitative electroencephalogram for prediction of delayed ischemia in subarachnoid haemorrhage: report of one case

Subarachnoid hemorrhage (SAH) is a devastating disease, with a mortality rate of 35%. Among patients who survive the initial bleeding, the leading cause of morbidity and mortality is delayed cerebral ischemia (DCI). Electroencephalography (EEG) can detect cerebral ischemia in the early stages. We report a 66-year-old female patient who consulted for ictal headache and impaired consciousness. On admission, she was confused, dysarthric, and with meningeal signs. Brain angio-CT showed SAH FISHER IV and an aneurysm of the left posterior cerebral artery. After excluding the aneurysm (by coiling), the patient recovered the altered consciousness. Continuous EEG monitoring was initiated. On the sixth day of follow up, she had a transient headache and apathy. The brain MRI showed low cerebral blood flow in the left frontotemporal area, without ischemic lesions. On the seventh day, she presented expression aphasia and right facial-brachial paresis. Angiography confirmed severe vasospasm in M1 and M2 segments bilaterally. Pharmacological angioplasty with nimodipine was performed, with an excellent radiological response, although not clinical. A second MRI was carried out on the eighth day, which showed a left insular infarction and generalized vasospasm. A second therapeutic angiography was performed; the patient persisted with aphasia and left central facial paresis. The quantitative EEG analysis performed retrospectively showed a generalized reduction in the spectral edge frequency 95 (SEF95; meaning slowing in the EEG signal) at the fourth day of follow up, three days earlier than the clinical and imaging diagnosis of DCI was established.

Effect of racial background on motor cortical function as measured by threshold tracking transcranial magnetic stimulation.

A previous study using traditional paired-pulse TMS methods (amplitude-tracking) has reported differences in resting motor threshold (RMT) and short-interval intracortical inhibition (SICI) between healthy subjects of Caucasian and Han Chinese backgrounds, probably due to differences in the skull shape. The amplitude-tracking method delivers stimuli with constant intensity and causes substantial variabilities in motor-evoked potential amplitudes. To overcome this variability, threshold tracking transcranial magnetic stimulation (TT-TMS) has been developed. The present study aimed to investigate whether racial differences in motor cortical function exist, using TT-TMS. A total of 83 healthy volunteers (30 Caucasians, 25 Han Chinese, and 28 Japanese) were included in the present series. In TT-TMS and nerve conduction studies, electrodes were placed on the dominant limb, with measures recorded from the abductor pollicis brevis muscle. Stimulations were delivered with a circular coil, directly above the primary motor cortex. There were no significant differences at all the SICI intervals between races. Similarly, there were no significant differences in other measures of excitability including mean RMT, intracortical facilitation, and cortical silent period. Contrary to traditional amplitude-tracking TMS, motor cortical excitability and thereby motor cortical function is minimally influenced by racial differences when measured by TT-TMS. Recent studies have disclosed that SICI measured by TT-TMS differentiates amyotrophic lateral sclerosis (ALS) from ALS mimic disorders, with high sensitivity and specificity, in Caucasians. This study suggested that TT-TMS can be applied for the ALS diagnosis in Asian patients, as well as Caucasians.NEW & NOTEWORTHY Threshold tracking transcranial magnetic stimulation (TT-TMS) was applied for Caucasians, Han Chinese, and Japanese. No significant differences were found in TMS excitability indexes among races. Recent studies have disclosed that TT-TMS indexes differentiate amyotrophic lateral sclerosis (ALS) from ALS mimic disorders, with high sensitivity and specificity, in Caucasians. This study suggested that TT-TMS can be applied for the ALS diagnosis in Asian patients, as well as Caucasians.

Encefalopatía subaguda en una paciente con policondritis recidivante: caso clínico / Subacute encephalopathy associated with relapsing polychondritis: report of one case

Relapsing polychondritis (RP) is a rare multisystemic autoimmune disorder characterized by the inflammation and destruction of cartilages, with preference for auricular, nasal and laryngotracheal cartilages. RP may also affect proteoglycan-rich structures, such as, blood vessels, eyes, kidneys, and heart. The central nervous system (CNS) is involved in less than 3% of patients. We report a 32-year-old female with RP associated with a progressive subacute encephalopathy characterized by behavioral disturbances, auditory and visual hallucinations. The EEG showed generalized slow activity and a mononuclear pleocytosis with increased protein was found in the cerebrospinal fluid. The brain magnetic resonance imaging showed multiple supra and infratentorial nodular inflammatory lesions. After initiating treatment with corticosteroids and cyclophosphamide, a significant improvement in chondritis and neurological status was observed.

[Monomelic amyotrophy. Report of one case]. / Atrofia monomiélica distal de extremidad superior. Caso clínico.

Monomelic amyotrophy, also known as Hirayama disease, is a rare lower motor neuron syndrome due to localized lower motor neuron loss in the spinal cord at the cervical level. Clinically, monomelic amyotrophy is defined by the insidious onset of unilateral atrophy and weakness involving the hand and forearm, typically beginning in the second or third decade of life. We report 19-year-old man with a two years history of slowly progressive unilateral weakness and atrophy of his right-hand muscles. Neurological examination revealed weakness and atrophy in his intrinsic hand muscles, with sparing of the abductor pollicis brevis muscle. Also, mild atrophy of the ulnar aspect of the forearm was detected with sparing of the brachioradialis muscle. Electromyography showed active and chronic neurogenic changes affecting C8 and T1 myotomes, with mild chronic neurogenic changes on C7 myotome. Magnetic resonance imaging of his cervical spine revealed spinal cord atrophy involving C5 to C7 segments, associated with forward displacement of the posterior wall of the dura in cervical spine flexion. The clinical features associated with the imaging and electrophysiological findings support the diagnosis of monomelic amyotrophy.

Atrofia monomiélica distal de extremidad superior. Caso clínico

Monomelic amyotrophy, also known as Hirayama disease, is a rare lower motor neuron syndrome due to localized lower motor neuron loss in the spinal cord at the cervical level. Clinically, monomelic amyotrophy is defined by the insidious onset of unilateral atrophy and weakness involving the hand and forearm, typically beginning in the second or third decade of life. We report 19-year-old man with a two years history of slowly progressive unilateral weakness and atrophy of his right-hand muscles. Neurological examination revealed weakness and atrophy in his intrinsic hand muscles, with sparing of the abductor pollicis brevis muscle. Also, mild atrophy of the ulnar aspect of the forearm was detected with sparing of the brachioradialis muscle. Electromyography showed active and chronic neurogenic changes affecting C8 and T1 myotomes, with mild chronic neurogenic changes on C7 myotome. Magnetic resonance imaging of his cervical spine revealed spinal cord atrophy involving C5 to C7 segments, associated with forward displacement of the posterior wall of the dura in cervical spine flexion. The clinical features associated with the imaging and electrophysiological findings support the diagnosis of monomelic amyotrophy.

[Fasciculations and cramps: physiological bases and clinical approach of a complex phenomenon]. / Fasciculaciones y calambres: bases fisiológicas y enfrentamiento clínico de un fenómeno complejo.

Fasciculations and cramps originate in the motor unit, a functional unit that includes the lower motor neuron and their innervated muscle fibres. Both are common complaints in outpatient practice. These symptoms can be secondary to neurological or medical pathology, presenting a broad differential diagnosis and a complex approach. Recent neurophysiological studies have increased the knowledge of their origin mainly in amyotrophic lateral sclerosis. The symptomatic management of fasciculations and cramps depends on their etiology and includes pharmacological and non-pharmacological treatments. This article aims to present an updated review of the most relevant aspects of physiopathology, clinical approach, and differential diagnosis of both phenomena.

[Quantitative electroencephalogram for prediction of delayed ischemia in subarachnoid haemorrhage. Report of one case]. / Electroencefalograma cuantitativo en la predicción precoz de la isquemia cerebral tardía en hemorragia subaracnoidea aneurismática.Reporte de un caso.

Subarachnoid hemorrhage (SAH) is a devastating disease, with a mortality rate of 35%. Among patients who survive the initial bleeding, the leading cause of morbidity and mortality is delayed cerebral ischemia (DCI). Electroencephalography (EEG) can detect cerebral ischemia in the early stages. We report a 66-year-old female patient who consulted for ictal headache and impaired consciousness. On admission, she was confused, dysarthric, and with meningeal signs. Brain angio-CT showed SAH FISHER IV and an aneurysm of the left posterior cerebral artery. After excluding the aneurysm (by coiling), the patient recovered the altered consciousness. Continuous EEG monitoring was initiated. On the sixth day of follow up, she had a transient headache and apathy. The brain MRI showed low cerebral blood flow in the left frontotemporal area, without ischemic lesions. On the seventh day, she presented expression aphasia and right facial-brachial paresis. Angiography confirmed severe vasospasm in M1 and M2 segments bilaterally. Pharmacological angioplasty with nimodipine was performed, with an excellent radiological response, although not clinical. A second MRI was carried out on the eighth day, which showed a left insular infarction and generalized vasospasm. A second therapeutic angiography was performed; the patient persisted with aphasia and left central facial paresis. The quantitative EEG analysis performed retrospectively showed a generalized reduction in the spectral edge frequency 95 (SEF95; meaning slowing in the EEG signal) at the fourth day of follow up, three days earlier than the clinical and imaging diagnosis of DCI was established.